Neurophysiological characterisation of neurons in the rostral nucleus reuniens in health and disease

• Main Author: Walsh, Darren
• Other Authors: Randall, Andrew ; Brown, Jon
• Published: University of Exeter 2017
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.743986

Evidence is mounting for a role of the nucleus reuniens (Re) in higher cognitive function. Despite growing interest, very little is known about the intrinsic neurophysiological properties of Re neurons and, to date, no studies have examined if alterations to Re neurons may contribute to cognitive deficits associated with normal aging or dementia. Work presented chapter 3 provides the first detailed description of the intrinsic electrophysiological properties of rostral Re neurons in young adult (~5 months) C57-Bl/6J mice. This includes a number of findings which are highly atypical for thalamic relay neurons including tonic firing in the theta frequency at rest, a paucity of hyperpolarisation-activated cyclic nucleotide–gated (HCN) mediated currents, and a diversity of responses observed in response to depolarising current injections. Additionally this chapter includes a description of a novel form of intrinsic plasticity which alters the functional output of Re neurons. Chapter 4 investigates whether the intrinsic properties of Re neurons are altered in aged (~15 month) C57-Bl/6J mice as compared to a younger control group (~5 months). The intrinsic properties were remarkably similar across age ranges suggesting that alterations to the intrinsic properties of Re neurons do not contribute to age-related cognitive deficits. Chapter 5 investigates whether alterations to the intrinsic properties of Re neurons occur in the J20 model of amyloidopathy. Alterations to the resting membrane potential (RMP), propensity to rebound fire, and a reduction in action potential (AP) width were observed. This suggests that alterations to the intrinsic properties of Re neurons may contribute to cognitive deficits observed in Alzheimer’s disease (AD). Chapter 6 investigates whether alterations to the intrinsic properties of Re neurons occur in a mouse model (CHMP2Bintron5) of frontotemporal dementia (FTD). Only subtle changes were observed suggesting that alterations to the intrinsic properties of Re neurons does not contribute to cognitive deficits observed in FTD linked to chromosome 3 (FTD-3).